Interview with Dr. Wild in Le Monde

On the occasion of the investigation published by Le Monde on Tuesday, October 25, regarding the figures concerning cancer in France, Christopher Wild, director of the International Agency for Research on Cancer [IARC, the cancer agency of the World Health Organization headquartered in Lyon] , explains the overall patterns of the evolution of malignant tumors in the world…

What are the overall tendencies in the global evolution of the incidence of cancer?

We do not currently have solid data on the long term evolution of the incidence of cancer for all countries. This information, obtained from nationally registered data, remains scarce in numerous developing countries. Starting from the database of the IARC, we observe changes linked to development: the level of occurrence of certain major cancers (lung, breast, colorectal) is increasing in many poor or emerging countries, while several others, more associated with poverty or infectious diseases (uterus, stomach, liver) seem, rather, to be on the decline.

Overall, an understanding of those incidences which are increasing in countries in transition has to do with changes in the risks undertaken, which are approaching those of the rich countries: tobacco consumption, overweight, sedentary, increase in the age of child bearing and breast feeding… For several cancers a divergence in global tendencies can be observed: among men, lung cancer tends to decline in wealthier countries but is stable or still increasing among women.

These tendencies reflect the “maturity” of the epidemic of tobacco use, and the fact that women have taken up cigarettes more recently than men. Globally, in lower income countries the smoking habit has arrived later and we may be able to observe in decades to come a rapid increase in cancer in certain countries, particularly among men. Other cancers are increasing as well: a sub-type of cancer of the esophagus strongly linked to obesity is increasing in several western countries.

How is the sharp increase in the incidence of thyroid cancer to be interpreted?

These increases are linked to the development of new diagnostic tools (tomography, magnetic resonance imaging, etc.) which have led to a considerable augmentation in the detection of small papillary tumors, which would not have been evident before.

In spite of a decline at the world wide level, cancer of the cervix is still increasing in certain countries of East Africa, Eastern Europe and in the former Soviet countries.

The incidence of a good number of cancer types is at the same time reasonably constant. The mortality rate of pancreatic cancer is relatively stable, for example. But because of the poor prognosis of these tumors and advances in the treatment of other major forms of cancer (breast, prostate, colorectal), this illness [pancreatic cancer] has become one of the leading causes of death in the EU countries.

Beyond the big, known causes – tobacco, alcohol – what are the major determining factors observed?

We now have considerable knowledge of certain risk factors, that can explain part of the developments under observation: First of all, the impact of chronic infections is often neglected as a risk factor, but accounts for perhaps 15% of cancer at a global level, especially for liver cancer (viral hepatitis), cervical cancer (papillomavirus) and stomach cancer (Helicobacter pilori).

However, this varies considerably country by country: in Africa more than 40% of cancers are linked to such infections, against 1% to 3% in North America or Australia, for example… Certain viral or bacterial infections decrease along with the level of development.

It is also interesting to see, in certain wealthy countries, the increase in the number of cancers in the oropharyngeal (mouth, lips, pharynx, etc.) and ano-genital areas associated with sexual transmission of human papillomavirus (HPV). This development is a supplementary argument for the introduction of the HPV vaccine, the benefits of which will extend beyond the prevention of cervical cancer.

What are the consequences of the increase in tobacco use?

Tobacco use continues to increase in numerous countries, which leads naturally to a rise in the incidence of lung and other cancers, including a pronounced increase among women as well as men, as well as other health effects (cardiovascular illness, chronic respiratory trouble, etc.)

Overweight, obesity and lack of physical activity are increasing in a dramatic manner in numerous regions of the world and these life style changes are associated with accumulated risk of several cancers, among which are breast, esophagus, colorectal, kidney…

To what are these life style changes connected?

They are often linked to urbanization, diet, sugary drinks and to the consumption of red meat and processed meats. At the same time, the tendency for women to have children later in life, to have fewer children and to breast feed only for short periods of time is associated with the increase in the incidence of breast cancer in numerous countries.

Has not classic oncology, founded before all else on the concept of mutation, been overtaken by the emergence of new toxicological paradigms?

I would certainly not say that the concept of mutation [of a cell – LeM] has been, one way or another, made obsolete by recent advances in the understanding of molecular mechanisms facilitating cancer. Cancers are to the contrary characterized by a large number of mutations.

I would further say that the discovery of new “events” at the molecular or cellular level which lead to the development of a cancer come with and complement the fundamental work undertaken on mutations and offer fantastic opportunities to study the prevention, the early detection and treatment of this illness.

It is very stimulating to witness the arrival of new tools for the investigation of different “events” – as for example epigenetic modifications [certain changes in DNA or in the genetic environment – LeM] which may be produced among populations.

One of the critical challenges with which we are confronted is to understand how, beyond the induction of mutations, environmental or behavioral factors have an impact on the risk of developing cancer. This information is fundamental for prevention and early detection and has been until the present time largely neglected, compared to other domains of cancer research.

Has not the epidemiology of cancer arrived at a limit, in fact, at the current time, on the effects of environmental factors – as, for example, exposure to toxic chemicals – during critical periods of development such as fetal, perinatal, adolescence – which may, in the majority of cases, be accounted for?

Take care: it would be a mistake to believe that exposure during adult life might be without importance or necessarily less important than exposure during the perinatal period. However, epidemiology must certainly consider life taken as a whole and must measure exposure during all periods of life, as accurately as possible, while using the most feasible instruments, such as questionnaires, environmental measurements or biological markers, for example.

I do not think that exposure during adolescence or in the period around birth cannot be measured, but I recognize that to obtain accurate measurements is certainly a challenge to the extent that the exposure occurred in the past. The encouraging news is that new scientific developments will permit meeting this challenge.

What are they?

I will cite two: The first is that certain environmental exposures leave a molecular “tattoo” in DNA – in the blood cells, or in the tumor itself, for example – that can be detected many years after expression. This allows the beginning of an opening of a window into the past.

The second is that there are in the world a large number of recruited individuals from mother-father-children cohorts, who provide biological samples. In these studies it is possible to link exposures in the perinatal period with changes in the biology of the child.

One might then interpret these observations in connection with abnormalities of cellular or molecular function observed later in life. There again, this will allow the establishment of a bridge between an event that occurred early in life and its consequences much later.

This is Bill Spurlin’s translation of an interview given by Dr Christopher Wild to Le Monde, published here without objection from the IARC.

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